Six normal subjects and nine patients with suspected sensitivity to aspartame have participated in a NIAID-CRS approved blind challenge protocol. Two patients with a history of aspartame sensitivity had a positive skin test to aspartame. One individual with a history of adverse reactions developed several hives during single- but not double-blind challenge. Plasma histamine levels remained normal in all cases. Hypersensitivity to aspartame thus appears infrequent. Two normal subjects, two asthmatics, and one individual with a history of hives from MSG have participated in a NIAID-CRS approved protocol for MSG sensitivity. No adverse responses were noted to MSG, and no changes occurred in plasma histamine levels. The "Chinese Restaurant Syndrome" was not observed. Neither MSG nor aspartame was capable of provoking mast cell or basophil degranulation in vitro at nontoxic levels. On a collaborative project with Dr. P. V. Subba Rao at the Indian Institute of Science, we have demonstrated IgE directed to shrimp-derived tRNA in the sera of two patients with shrimp allergy. This represents the first demonstration of tRNA as an allergen.